Author | Hayashi, Elize A. | |
Author | Granato, Alessandra | |
Author | Paiva, Luciana S. | |
Author | Bertho, Alvaro L. | |
Author | Bellio, Maria | |
Author | Nobrega, Alberto | |
Access date | 2018-05-10T14:13:59Z | |
Available date | 2018-05-10T14:13:59Z | |
Document date | 2010 | |
Citation | HAYASHI, Elize A. et al. TLR4 Promotes B Cell Maturation: Independence and Cooperation with B Lymphocyte-Activating Factor. J Immunol., v.184, p.4662-4672, Mar. 2010. | pt_BR |
ISSN | 0022-1767 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/26373 | |
Language | eng | pt_BR |
Publisher | American Association of Immunologists | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | ativação de linfócitos B | pt_BR |
Subject in Portuguese | maturação de células B | pt_BR |
Subject in Portuguese | Receptor 4 Toll-Like | pt_BR |
Title | TLR4 promotes B cell maturation: independence and cooperation with B lymphocyte-activating factor | pt_BR |
Type | Article | pt_BR |
DOI | 10.4049/jimmunol.0903253 | |
Abstract | We have previously shown that TLR4 triggering promotes the generation of CD23(+)CD93(+) transitional T2-like cells in vitro from mouse B cell precursors, suggesting a possible role for this receptor in B cell maturation. In this study, we perform an extensive study of cell surface markers and functional properties of B cells matured in vitro with LPS, comparatively with the well-known B cell maturation factor B lymphocyte-activating factor (BAFF). LPS increased generation of CD23(+) transitional B cells in a TLR4-dependent way, upregulating IgD and CD21 and downregulating CD93, without inducing cell proliferation, in a manner essentially equivalent to BAFF. For both BAFF and LPS, functional maturation of the IgM(+)CD23(+)CD93(+) cells was confirmed by their higher proliferative response to anti-CD40 plus IL-4 compared with IgM(+)CD23(neg)CD93(+) cells. BAFF-R-Fc-mediated neutralization experiments showed that TLR4-induced B cell maturation was independent of BAFF. Distinct from BAFF, maturation by LPS relied on the activation of canonical NF-kappaB pathway, and the two factors together had complementary effects, leading to higher numbers of IgM(+)CD23(+)CD93(+) cells with their simultaneous addition. Importantly, BCR cross-linking abrogated the generation of CD23(+) B cells by LPS or BAFF, indicating that signals mimicking central tolerance act on both systems. Addition of cyclosporin A reverted BCR-mediated inhibition, both for BAFF and LPS, suggesting similar regulation of signaling pathways by calcineurin. Finally, LPS-injected mice showed a rapid increase of mature B cells in the bone marrow, suggesting that TLR4 signaling may effectively stimulate B cell maturation in vivo, acting as an accessory stimulus in B cell development, complementary to the BAFF physiological pathway. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunobiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunobiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunobiologia. Rio de Janeiro, RJ, Brasil / Universidade Federal Fluminense. Instituto de Biologia. Departamento de Imunobiologia. Rio de Janeiro, RJ, Brasil | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Citometria de Fluxo. Rio de Janeiro, RJ. Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunobiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Microbiologia. Departamento de Imunobiologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | TLR4 | pt_BR |
Subject | B Cell Maturation | pt_BR |
Subject | B Lymphocyte | pt_BR |
Subject | Activating Factor | pt_BR |
e-ISSN | 1550-6606 | |
Embargo date | 2030-01-01 | |